Partial Seizures Research Articles

The sixth sense: how much does interictal intracranial EEG add to determining the focality of epileptic networks?

Intracranial EEG is used for two main purposes: to determine (i) if epileptic networks are amenable to focal treatment and (ii) where to intervene. Currently, these questions are answered qualitatively and differently across centres. There is a need to quantify the focality of epileptic networks systematically, which may guide surgical decision-making, enable large-scale data analysis and facilitate multi-centre prospective clinical trials. We analysed interictal data from 101 patients with drug-resistant epilepsy who underwent pre-surgical evaluation with intracranial EEG at a single centre. We chose interictal data because of its potential to reduce the morbidity and cost associated with ictal recording. Sixty-five patients had unifocal seizure onset on intracranial EEG, and 36 were non-focal or multi-focal. We quantified the spatial dispersion of implanted electrodes and interictal intracranial EEG abnormalities for each patient. We compared these measures against the '5 Sense Score,' a pre-implant prediction of the likelihood of focal seizure onset, assessed the ability to predict unifocal seizure onset by combining these metrics and evaluated how predicted focality relates to subsequent treatment and outcomes. The spatial dispersion of intracranial EEG electrodes predicted network focality with similar performance to the 5-SENSE score [area under the receiver operating characteristic curve = 0.68 (95% confidence interval 0.57, 0.78)], indicating that electrode placement accurately reflected pre-implant information. A cross-validated model combining the 5-SENSE score and the spatial dispersion of interictal intracranial EEG abnormalities significantly improved this prediction [area under the receiver operating characteristic curve = 0.79 (95% confidence interval 0.70, 0.88); P < 0.05]. Predictions from this combined model differed between surgical- from device-treated patients with an area under the receiver operating characteristic curve of 0.81 (95% confidence interval 0.68, 0.85) and between patients with good and poor post-surgical outcome at 2 years with an area under the receiver operating characteristic curve of 0.70 (95% confidence interval 0.56, 0.85). Spatial measures of interictal intracranial EEG abnormality significantly improved upon pre-implant predictions of network focality by area under the receiver operating characteristic curve and increased sensitivity in a single-centre study. Quantified focality predictions related to ultimate treatment strategy and surgical outcomes. While the 5-SENSE score weighed for specificity in their multi-centre validation to prevent unnecessary implantation, sensitivity improvement found in our single-centre study by including intracranial EEG may aid the decision on whom to perform the focal intervention. We present this study as an important step in building standardized, quantitative tools to guide epilepsy surgery.

A randomized, double-blind, placebo-controlled, dose-escalating phase IIa trial to evaluate the safety, tolerability, efficacy, and pharmacokinetics of multiple oral doses of Pynegabine tablets as add-on therapy in patients with focal epilepsy.

This study aims to investigate the safety, tolerability, efficacy, and pharmacokinetics of Pynegabine as an add-on therapy in the treatment of focal epilepsy. This is a protocol phase-IIa, randomized, double-blinded, placebo-controlled, multicenter study in patients with focal epilepsy from multiple centers in China who have been treated with at least 2 ASMs without effective control. The study involves an 8-week run-in period with stable use of previous medications. Patients are then randomized to receive either Pynegabine or a placebo. Sentinel administration is performed initially, and subsequent patients are randomized based on safety assessments. Three dose cohorts (15, 20, and 25 mg/d) are established. Efficacy is assessed through various measures, including seizure frequency, CGI score, PGI score, HAMA score, HAMD score, MoCA scale score, QOLIE-31 scale score, and 12 h-EEG score. Safety evaluations, PK blood samples, concomitant medications, and adverse events are also recorded. Data from the study will be used to evaluate the safety, tolerability, efficacy, and pharmacokinetics of Pynegabine tablets as add-on therapy for focal epilepsy.

Deep brain stimulation targets in drug-resistant epilepsy: Systematic review and meta-analysis of effectiveness and predictors of response

PurposeAnterior nucleus of the thalamus (ANT) is the only deep brain stimulation (DBS) target that is approved by the FDA for treatment of drug-resistant epilepsy (DRE). Hippocampus (HC) and centromedian nucleus (CMN) have been reported as potential DBS targets for DRE. This study aimed to assess the effectiveness and predictors of response among DRE patients treated with DBS in general and among ANT, HC and CMN DBS-targets. MethodsA systematic search was executed on PubMed, SCOPUS and the Cochrane Central Register of Controlled Trials (CENTRAL) electronic databases between Jan 1, 2000 and June 29, 2020. Patients with DRE who underwent DBS treatment with at least three months of follow-up were included. Individual patient data (IPD) meta-analysis was conducted on DBS studies with available IPD. Response was defined as ≥50 % reduction in seizures frequency. Responders group was compared with non-responders group in terms of demographics, epilepsy/seizure characteristics, MRI findings, and DBS targets and duration of use. Subsequently, predictors of response to different DBS targets were investigated. ResultsThirty-nine studies with a total of 296 patients (ANT: 69 %, HC: 11 %, CMN: 21 %) were included. The responders group constituted of 209 patients (70.6 %). The response was significantly higher in patients with generalized seizures compared to those with focal seizures (93.2% vs 63.9 %; p < 0.001). Response was significantly higher with CMN (83.9 %) and HC (77.4 %) compared with ANT (65.5 %) as DBS targets (p = 0.014). Response was also significantly associated with longer duration of DBS use (p = 0.008). The responder rate was higher among the patients with lesional MRIs (76.7 %) than those with non-lesional MRIs (66.7 %), but with no statistically significant difference (p = 0.134). Age, gender, epilepsy etiology, onset zone of focal seizures, and previous use of VNS had no significant differences between the responders and non-responders. A binary logistic regression including the seizure type, MRI findings, DBS targets, and DBS duration showed, after controlling for confounders, that the duration of DBS use was the only significant predictor of response (adjusted OR 1.061; 95 % CI 1.019–1.106; p = 0.005). Regarding DBS targets, the response rate in patients with symptomatic etiology was significantly higher with HC or CMN targets than the ANT (p = 0.003). In patients with non-lesional MRI, response rate was significantly higher with the CMN target compared to the other two targets (p = 0.008). ConclusionDBS proves to be effective in DRE, with progressive success upon longer treatment and possibility of improving quality of life. In addition to focal seizures, DBS has potential for treating generalized seizures as well. While the ANT stands as the most utilized and only approved DBS target for DRE, CMN and HC are alternative targets with high seizure control potential. Patients with symptomatic etiology showed significant seizure reduction when HC or CMN were targeted. Studies revealed noticeable effectiveness of CMN-DBS in treating patients with non-lesional MRI. Despite ANT prominence in research, our findings suggest promising outcomes with CMN and HC, emphasizing the need for future larger-scale comparative clinical trials to better understand the efficacy of different DBS targets.

Long-term Effect of Multichannel tDCS Protocol in Patients with Central Cortex Epilepsies Associated with Epilepsia Partialis Continua.

Epilepsia partialis continua (EPC) is a rare type of focal motor status epilepticus that causes continuous muscle jerking in a specific part of the body. Experiencing this type of seizure, along with other seizure types, such as focal motor seizures and focal to bilateral tonic-clonic seizures, can result in a disabling situation. Non-invasive brain stimulation methods like transcranial direct current stimulation (tDCS) show promise in reducing seizure frequency (SF) when medications are ineffective. However, research on tDCS for EPC and related seizures is limited. We evaluated personalized multichannel tDCS in drug-resistant EPC of diverse etiologies for long-term clinical efficacy We report three EPC patients undergoing a long-term protocol of multichannel tDCS. The patients received several cycles (11, 9, and 3) of five consecutive days of stimulation at 2mA for 2 × 20min, targeting the epileptogenic zone (EZ), including the central motor cortex with cathodal electrodes. The primary measurement was SF changes. In three cases, EPC was due to Rasmussen's Encephalitis (case 1), focal cortical dysplasia (case 2), or remained unknown (case 3). tDCS cycles were administered over 6 to 22 months. The outcomes comprised a reduction of at least 75% in seizure frequency for two patients, and in one case, a complete cessation of severe motor seizures. However, tDCS had no substantial impact on the continuous myoclonus characterizing EPC. No serious side effects were reported. Long-term application of tDCS cycles is well tolerated and can lead to a considerable reduction in disabling seizures in patients with various forms of epilepsy with EPC.

Interictal psychosis of epilepsy: What is the role of the neurologist?

Psychotic disorders are more frequent in people with epilepsy than the general population. They constitute one of the most serious psychiatric comorbidities which require an immediate psychopharmacologic intervention. Yet, access to psychiatrists is often limited or not available and the neurologists taking care of these patients are called-upon to start treatment with antipsychotic medication. The purpose of this manuscript is to provide clinicians with pragmatic psychopharmacologic strategies to treat interictal psychotic disorders in patients with epilepsy. We review the case of a 45 years-old man with a 35-year history of treatment-resistant focal epilepsy of bitemporal origin who developed a de-novo psychotic episode that began with insomnia, mood lability and agitation and evolved into paranoid delusions, auditory hallucinations and a thought disorder. The patient was diagnosed with an interictal psychotic episode and was treated with aripiprazole which resulted in significant improvement after reaching a 20 mg /day dose and allowed for the patient to be discharged home. In summary, interictal psychotic episodes of epilepsy are relatively frequent in patients with epilepsy and require of an early psychopharmacologic treatment to facilitate their remission or stabilization until mental health professionals can take over their long-term care. Compared to primary psychotic disorders, interictal psychotic episodes respond better and at lower doses of antipsychotic drugs.

Causal association between epilepsy and its DNA methylation profile and atrial fibrillation

BackgroundThe "epileptic heart" concept is emerging, but the causal relationship between epilepsy and atrial fibrillation (AF) remains unclarified. ObjectiveThis study explores the genetic correlations and bidirectional causality between various epilepsy phenotypes and AF. MethodsGenome-wide association study (GWAS) statistics for 10 epilepsy subtypes (29,944 cases, 52,538 controls) and AF (60,620 cases, 970,216 controls) were sourced from the International League Against Epilepsy (ILAE) and HGRI-EBI Catalog-GWAS, respectively. Linkage disequilibrium score regression (LDSC) and genome-wide Mendelian Randomization (MR) evaluated genetic correlations and bidirectional causal relationships. Epilepsy-related DNA methylation data (N= ∼800) from EWAS catalog were analyzed to identify causal CpG sites influencing AF risk through epigenetic MR. ResultsLDSC revealed significant genetic correlations between four epilepsy subtypes and AF (rg from 0.116 to 0.241). Forward MR suggested a significant causal effect of focal epilepsy with hippocampal sclerosis (FE with HS) on AF risk (IVW and MR-PRESSO: OR = 1.046, P ≤ 0.004), with results robust against heterogeneity, horizontal pleiotropy, and outliers. Epigenetic MR indicated that lower methylation at cg06222062 (OR = 0.994, P = 3.16E-04) mapped to PLA2G5 and cg08461451 mapped to SPPL2B gene (OR = 0.954, P = 1.19E-03), and higher cg10541930 in the C10orf143 promoter (OR = 1.043, P = 4.18E-22) increases AF risk. Sensitivity analyses affirmed no pleiotropic bias. ConclusionFE with HS significantly increases AF risk, highlighting the natural neural-cardiac connection and the need for cardiac monitoring in epilepsy patients. Specific methylated CpG sites may serve as biomarkers and preventive targets for AF susceptibility.

Resective surgery for mesial temporal lobe epilepsy associated with hippocampal sclerosis in patients over 50 years: a case-control study.

Mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE/HS) is the most common cause of drug-resistant focal seizures and surgical resection is the primary treatment option, with seizure-free rates ranging from 60 to 80%. However, data on postsurgical seizure outcomes in patients ≥ 50years of age are limited. This study aimed to assess the efficacy and safety of surgery in this age group compared to younger patients. We performed a retrospective analysis of data from resective surgeries conducted in patients with MTLE/HS between 1990 and 2022. We focused on patients aged ≥ 50years and compared the surgical safety and efficacy variables between this group and a control group of patients aged < 50years through a case-control study. Among the 450 MTLE/HS patients who underwent surgery during the inclusion period, 61 (13.6%) were aged ≥ 50years and matched with 183 younger patients, totaling 244 study participants. The two groups had similar characteristics. At the last follow-up (median 5.7years), Engel I outcomes were achieved in 80.3% of the older patients and 81.4% of the younger patients, with no significant difference (p = 0.85). Postoperative cognitive and psychiatric outcomes did not differ between the groups. Major complication rates were also comparable, at 3.3% in the older group and 2.7% in the younger group (p = 0.83). The extratemporal ictal abnormalities observed on video-EEG were the only variable that demonstrated a significant association with an unfavorable seizure outcome in the older group (OR 9.3, 95% CI [1.8-47.6], p = 0.005). This study provides grade 3 evidence that resective surgery for MTLE/HS patients aged ≥ 50years is as effective and safe as it is for younger patients, and thus should be considered as the primary treatment option for drug-resistant cases.

Next-generation sequencing in pediatric-onset epilepsies: Analysis with target panels and personalized therapeutic approach.

The objective of this study is to report the results of the genetic analysis in a large and well-characterized population with pediatric-onset epilepsies and to identify those who could benefit from precision medicine treatments. In this retrospective observational study, we consecutively recruited patients with pediatric-onset epilepsy observed at a tertiary neurological center over a time span of 7 years, collecting clinical and laboratory findings. Following in-depth diagnostic process to exclude possible structural and metabolic causes of the disease, patients with a suspected genetically determined etiology underwent next-generation sequencing (NGS) screening with panels for the analysis of target genes causative of epilepsy. We detected likely pathogenic or pathogenic variants (classes IV and V) in 24% of the 562 patients who underwent genetic investigations. By the evaluation of patients' data, we observed that some features (onset of epilepsy before one year old, presence of neurological deficits, psychomotor delay/cognitive disability, and malformative aspects at brain MRI) were significantly associated with class IV or V variants. Moreover, statistical analysis showed that the diagnostic yield resulted higher for patients affected by Progressive Myoclonic Epilepsy (PME) and with early onset developmental and epileptic encephalopathies (DEE), compared with focal epilepsies, genetic generalized epilepsies, DEE with onset at/after 1 y.o., and unclassified epileptic syndromes. According to the results of the genetic screening, up to 33% of patients carrying class IV or V variants resulted potentially eligible for precision medicine treatments. The large-scale application of NGS multigene panels of analysis is a useful tool for the molecular diagnosis of patients with pediatric-onset epilepsies, allowing the identification of those who could benefit from a personalized therapeutic approach. The analysis of patients with pediatric-onset epilepsy using advanced technologies for the screening of all the implicated genes allows the identification of the cause of diseases in an ever-increasing number of cases. Understanding the pathogenic mechanisms could, in some cases, guide the selection and optimization of appropriate treatment approaches for patients.

Brivaracetam use in children with epilepsy: A retrospective multicenter study

PurposeThis retrospective multicenter study aimed to assess the efficacy and safety of brivaracetam (BRV) in pediatric epilepsy. MethodsOur cohort consisted of 93 children (mean age 11.5 ± 7.5 years) with a wide spectrum of pediatric epilepsy, including epileptic encephalopathy and generalized epilepsy. Of these, 61 (60.4%) were diagnosed with focal epilepsy, 19 (15.8%) with generalized epilepsy, and 16 (15.8%) with combined epilepsy, while 8 patients (7.9%) had an unknown epilepsy type. The cohort included rare epilepsy syndromes: 8 patients with Lennox-Gastaut syndrome, 3 with Dravet syndrome, and 1 with Rasmussen syndrome. Patients had a history of various antiseizure medications (ASMs) (6.42 ± 3.15), and on average, were being treated with more than two (2.57 ± 1.16) drugs at the time of BRV deployment. ResultsRetention rates were high, with 80.6% of patients adhering to treatment at 3 months, 66.7% at 6 months, and 45.2% at 12 months. In 29 patients (30.1%), BRV was added in an overnight switch from levetiracetam (LEV), resulting in a reduction of behavioral adverse effects (AEs) in 5 patients (17.2%). The response rate was 25.8% at 3 months, 16.1% at 6 months, and 17.2% at 12 months, with no responders in the epileptic encephalopathy group. Therapy tolerance was notable, with 70 patients (75.3%) reporting no AEs. Transient AEs occurred in 10 patients (10.7%), and in 13 cases (14.0%), the AEs warranted dose adjustment or discontinuation of BRV. ConclusionApproximately one-fifth of pediatric patients with drug-resistant epilepsy responded to BRV, with the best response observed in patients with focal seizures. However, the impact on patients with epileptic encephalopathy was limited.

Transient alteration of Awareness triggered by direct electrical stimulation of the brain

BackgroundAwareness is a state of consciousness that enables a subject to interact with the environment. Transient alteration of awareness (AA) is a disabling sign of many types of epileptic seizures. The brain mechanisms of awareness and its alteration are not well known. Objective/HypothesisTransient and isolated AA induced by electrical brain stimulation during a stereoelectroencephalography (SEEG) recording represents an ideal model for studying the associated modifications of functional connectivity and locating the hubs of awareness networks. MethodsWe investigated the SEEG signals-based brain functional connectivity (FC) changes vs background occurring during AA triggered by three thalamic and two insular stimulations in three patients explored by SEEG in the frame of presurgical evaluation for focal drug-resistant epilepsy. The results were compared to the stimulations of the same sites that did not induce clinical changes (negative stimulations). ResultsWe observed decreased node strength in the pulvinar, insula, and parietal associative cortices during the thalamic and insular stimulations that induced AA. The link strengths characterizing functional coupling between the thalamus and the insular, prefrontal, temporal, or parietal associative cortices were also decreased. In contrast, there was an increased synchronization between the precuneus and the temporal lateral cortex. These FC changes were absent during the negative stimulations. ConclusionOur study highlights the role of the pulvinar, insular, and parietal hubs in maintaining the awareness networks and paves the way for invasive or non-invasive neuromodulation protocols to reduce AA manifestations during epileptic seizures.

Occipital lobe epilepsy surgery: treating seizures in the posterior cortex.

Occipital lobe epilepsy (OLE) is an uncommon type of extratemporal epilepsy constituting roughly 2-13% of symptomatic partial epilepsies and epilepsy surgery cases. Over two-thirds of patients with OLE present with two characteristics: (1) ictal semiology compatible with an occipital seizure focus (e.g., ictal blindness, visual perceptual disturbance, eye blinking, nystagmus), and (2) lateralizing features referable to the posterior cortex (e.g., visual field defects, contralateral head deviation). The remaining one-third of patients present with ≥ 2 seizure types, indicative of spread to other lobes. A common representation of this cortical spread is the altered mental status and generalized tonic-clonic activity seen in patient with OLE. While the key clinical symptoms include visual hallucinations, it may be difficult to elicit on history, especially from children, and are not always present.

Unforeseen outcomes: Unveiling cyst formation post stereotactic radiosurgery in brain arteriovenous malformations cases

IntroductionCyst formation after stereotactic radiosurgery (SRS) for brain arteriovenous malformations (AVMs) is a rare, delayed but important complication. Prompt recognition and appropriate treatment is essential for good outcome. MethodsWe analysed our institute’s Gamma knife treatment records from 2008 to 2023 and analysed AVM treated patients by gamma knife radiosurgery (GKRS). Patients with cyst formation and with adequate follow up were identified. Clinical details, management and prognosis of these patients was studied in detail along with prior literature review. ResultsA total of 921 AVM patients were treated in the above period and 7 patients were identified with cyst formation. The mean nidus volume was 12.98 ml, the mean radio surgical marginal dose was 23.57 Gy and maximal dose 47.21 Gy. The mean interval gap between SRS and cyst detection was 6.45 years. The mean volume of cyst cavity formed was 47.85 ml. Patients presented either with features of raised intracranial pressure (3) or focal neurological deficits (3) or seizures (1). 3 patients had achieved angiographic nidus obliteration at the time of cyst detection. Treatment was mostly on surgical lines with cyst fenestration(2 patients), excision (3 patients) and emergency decompressive craniectomy (1 patient). 1 patient required additional Ommaya insertion. Conservative management was followed for 1 patient. Residual nidus was treated either by concomitant excision or embolization or redo GKRS.Favourable outcome was seen in 6 out of 7 patients (85.71%) post cyst management with symptomatic and radiological improvement whereas 1 patient (14.28%) died due to refractory status epilepticus secondary to malignant cerebral edema. ConclusionCyst formation after GKRS for AVM treatment is an often-neglected complication due to its low incidence and often long latency period. Long term follow up of patients is hence necessary for prompt recognition. Diagnostic DSA should be done in all patients with cysts to look for residual nidus. Asymptomatic ones can be followed up conservatively while surgical treatment is required for symptomatic cases. Ventricular diversion like Ommaya or cystoperitoneal shunt may be necessary in some cases. Treatment outcome is usually favourable provided timely detection is done.

Epilepsy and Myasthenia Gravis: A Case Series.

The association between epilepsy and myasthenia gravis has rarely been reported, and when it has been reported, it has only been in a small case series. The aim of the present study was to report the frequency of epilepsy and myasthenia gravis and to describe a case series of patients with myasthenia gravis and epilepsy, focusing on their clinical characteristics and searching for a possible physiopathological mechanism. A retrospective, observational, adult center study was conducted in 2022. Patients were recruited from the database of the outpatient clinic of the Myasthenia Gravis and Epilepsy Unit of the Neurology Service, Hospital Universitari de Bellvitge. Five patients were included. The frequency of epilepsy in the myasthenia gravis cohort was 5/469 (1.1%), and the frequency of myasthenia gravis in the epilepsy cohort was 5/1432 (0.35%). All patients suffered from focal epilepsy, mainly temporo-central, which was drug-resistant in 3/5 Myasthenia gravis, which was generalized and with exacerbations in 3/5. Three patients were thymectomized (anatomopathology: thymic hyperplasia). Other autoimmune diseases were found in two (40%). Epilepsy onset preceded myasthenia gravis onset in all patients. Both diseases were considered autoimmune-related in 3/5, related to genetic predisposition due to altered innate immune system in 1/5, and due to chance or to treatment in 1/5. Epilepsy and myasthenia gravis are only infrequently associated. In adult patients, epilepsy onset precedes myasthenia onset in most cases. In some cases, epilepsy has an autoimmune etiology and coexists with other autoimmune conditions.

Seizure onset and offset pattern determine the entrainment of the cortex and substantia nigra in the nonhuman primate model of focal temporal lobe seizures.

Temporal lobe epilepsy (TLE) is the most common form of drug-resistant epilepsy. A major focus of human and animal studies on TLE network has been the limbic circuit. However, there is also evidence suggesting an active role of the basal ganglia in the propagation and control of temporal lobe seizures. Here, we characterize the involvement of the substantia nigra (SN) and somatosensory cortex (SI) during temporal lobe (TL) seizures induced by penicillin injection in the hippocampus (HPC) of two nonhuman primates. The seizure onset and offset patterns were manually classified and spectral power and coherence were calculated. We then compared the 3-second segments recorded in pre-ictal, onset, offset and post-ictal periods based on the seizure onset and offset patterns. Our results demonstrated an involvement of the SN and SI dependent on the seizure onset and offset pattern. We found that low amplitude fast activity (LAF) and high amplitude slow activity (HAS) onset patterns were associated with an increase in activity of the SN while the change in activity was limited to LAF seizures in the SI. However, the increase in HPC/SN coherence was specific to the farther-spreading LAF onset pattern. As for the role of the SN in seizure cessation, we observed that the coherence between the HPC/SN was reduced during burst suppression (BS) compared to other termination phases. Additionally, we found that this coherence returned to normal levels after the seizure ended, with no significant difference in post-ictal periods among the three types of seizure offsets. This study constitutes the first demonstration of TL seizures entraining the SN in the primate brain. Moreover, these findings provide evidence that this entrainment is dependent on the onset and offset pattern and support the hypothesis that the SN might play a role in the maintenance and termination of some specific temporal lobe seizure.

Deep brain stimulation of hippocampus in treatment of refractory temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most common cause of focal onset seizures, affecting 40% of adolescents and adults with epilepsy. TLE is also one of the most common drug resistant forms of epilepsy. Surgical resection remains the treatment of choice for TLE, but not all patients with TLE are suitable candidates for resective neurosurgery. For such patients, deep brain stimulation (DBS) of the hippocampus remains a reversible and efficient treatment alternative. We undertook a systematic review of the literature on hippocampal DBS efficacy and safety in the management of patients with TLE. A search using two electronic databases, the Medical Literature, Analysis, and Retrieval System on-line (MEDLINE) and the Cochrane Central Register of Controlled Trials (CEN-TRAL), was conducted. We found 14 articles related to hippocampal DBS for the treatment of TLE. The responder rate (defined as at least 50% reduction in seizure frequency) for all patients was 83.4%, Of 99 patients treated by hippocampal DBS, 82 were regarded as responders, and 17 as non-responders. Hippocampal DBS appears to be a safe and efficacious treatment alternative for patients who are not candidates for temporal lobectomy or selective amygdalohippocampectomy due to serious postoperative cognitive deficits. In selected patients with TLE, this neuromodulatory therapy may be very safe and efficacious.

Comparison of Premature Ejaculation in Men with Focal Epilepsy and Generalized Tonic-Clonic Epilepsy

Background: Premature ejaculation (PE) is a sexual disorder in men with significant prevalence among neurology patients. Epilepsy is one such condition where the prevalence of PE has been notably high. Objectives: This study aimed to compare the prevalence of PE in men with focal epilepsy and generalized tonic-clonic seizures (GTCS). Methods: In this cross-sectional observational study, 200 patients with epilepsy were included, with 100 patients having focal epilepsy and 100 patients having GTCS. The study utilized the demographic profile form, Men’s Sexual Health Questionnaire (MSHQ), Sexual Quality of Life-Men (SQOL-M), and premature ejaculation diagnostic tool (PEDT). Patients who visited specialized clinics and hospitals and met the inclusion criteria were recruited. Data were then analyzed using SPSS statistical software. Results: The results showed that the mean (SD) age of patients in the focal epilepsy group was 30.18 (3.85). The mean (SD) scores for the MSHQ, SQOL-M, and PEDT tools were 51.81 (11.98), 34.75 (9.36), and 8.63 (4.79), respectively. Although the mean (SD) PE score in the focal epilepsy group was 9.17 (4.49), higher than that of the GTCS group at 8.09 (5.04), the difference was not statistically significant. Additionally, there was a significant relationship between the PEDT score, SQOL-M score, and MSHQ score (P &lt; 0.05). The MSHQ and SQOL-M scores were lower in patients with PE disorder. Conclusions: Sexual disorders, including PE, are significantly prevalent in both groups of patients with epilepsy. Therefore, it is essential to implement both pharmacological and non-pharmacological interventions to reduce the incidence of PE in these patients.

Mapping Functional Connectivity Signatures of Pharmacoresistant Focal Cortical Dysplasia-Related Epilepsy.

To determine common network alterations in focal cortical dysplasia pharmacoresistant epilepsy (FCD-PRE) using functional connectivity analysis of resting-state functional magnetic resonance imaging (rsfMRI). This is a retrospective imaging cohort from Children's National Hospital (Washington, DC, USA) from January, 2011 to January, 2022. Patients with 3-T MRI-confirmed FCD-PRE underwent rsfMRI as part of routine clinical care. Patients were included if they were age 5-22 years at the time of the scan, and had a minimum of 18 months of follow-up. Healthy, typically-developing controls were included from Children's National Hospital (n = 16) and matched from Human Connectome Project-Development public dataset (n = 100). A total of 42 FCD-PRE patients (20 M:22 F, aged 14.2 ± 4.1 years) and 116 healthy controls (56 M:60 F, aged 13.7 ± 3.3 years) with rsfMRI were included. Seed-based functional connectivity maps were generated for each FCD, and each seed was used to generate a patient-specific z-scored connectivity map on 116 controls. FCD-PRE patients had mutual altered connectivity in regions of dorsal attention, default mode, and control networks. Functional connectivity was diminished within the FCD dominant functional network, as well as in homotopic regions. Cluster specific connectivity patterns varied by pathological subtype. Higher FCD connectivity to the limbic network was associated with increased odds of Engel I outcome. This study demonstrates diminished functional connectivity patterns in FCD-PRE, which may represent a neuromarker for the disease, independent of FCD location, involving the dorsal attention, default mode, and control functional networks. Higher connectivity to the limbic network is associated with a seizure-free outcome. Future multicenter, prospective studies are needed to allow for much earlier detection of signatures of treatment-resistant epilepsy. ANN NEUROL 2024.

Events of children responsible for the development of epilepsy in patients with cerebral palsy

Background: Cerebral palsy (CP) is characterized by abnormal muscle tone, ‘posture, and movement’, thereby limiting the activity of the affected person. Epilepsy is said to occur in 15-90% of children with CP. The aim of this study was to evaluate the events of children responsible for the development of epilepsy considering natal, postnatal characteristics and associated impairment in patients with CP. Methods: This was a case-control study and was conducted in the Department of Pediatric Neurology at the National Institute of Neurosciences and Hospital, Dhaka, Bangladesh during the period from January 2020 to December 2020. In total 150 children with cerebral palsy were enrolled in this study who were divided into two groups. In the ‘CP with epilepsy’ group, there were 50 patients, and in the CP without epilepsy group taken as a case group, there were 100 age-sex matched CP patients without epilepsy patients were taken as a control group. Informed written consent was taken from all the parents. Along with baseline characteristics, data regarding natal, postnatal events, general clinical findings, psychological assessment, computed tomography (CT) scan findings of the head, and electroencephalogram (EEG) findings in epilepsy cases were recorded in a predesigned questionnaire and analyzed. Results: In distributing the CP patients’ comparison regarding postnatal complications neonatal seizures were a strong predictor for epilepsy (p≤0.001). 1st seizure during 1st year of life and family history of epilepsy was also a significant event of epilepsy (p≤0.001). In the case of microcephaly, no significant difference was observed between groups (p=0.278). A significant difference was observed when the distribution of severity of intellectual disability of CP patients was compared between groups (p&lt;0.001). Abnormal CT scan findings of the head were significantly higher in CP with epilepsy 42 (84.0%) than in CP without epilepsy 46 (46.0%) (p≤0.001). The total mean age at the onset of epilepsy was 13.58±14.47 months. Epilepsy was most common in spastic quadriplegic CP (54%). 38.0% had focal epileptiform activity on EEG. Clinically focal epilepsy was found in 36.0% of cases. Conclusions: This study demonstrates the presence of a history of neonatal seizure, 1st seizure during 1st year of life, a family history of epilepsy, CT scan abnormalities, severe intellectual disability, and spastic quadriplegic CP were the events responsible for the development of epilepsy in children with CP.

Combined generalized and focal epilepsy with reflex features in Adaptor protein complex 4-associated hereditary spastic paraplegias: A cohort observational study

BackgroundPatients with genetic deficiency of the adaptor protein complex 4 (AP-4) exhibit earlyonset developmental delay, spastic diplegia, intellectual disability, speech impairment. The phenotype overlaps with other hereditary spastic paraplegias and cerebral palsies. Febrile seizures are common at onset. Epilepsy has been described in more than half of cases, arising in early infancy often with status epilepticus, but no typical seizure semiology or electroencephalographic features have been identified thus far. PurposeWe aimed to specifically investigate the epileptological characteristics of the syndrome to unveil possible biomarkers of seizure development and prognosis in AP-4 deficiency. MethodsObservational cohort study on patients with bi-allelic pathogenic variants in AP-4 subunits and epilepsy. We focused on the seizure semiology, electroencephalographic characteristics and response to antiseizure medications. ResultsPatients harboured pathogenic variants in AP4S1 (n = 5) or AP4M1 (n = 1). The phenotype included spastic paraparesis, intellectual disability, speech/language impairment, microcephaly, and MRI evidence of hypoplasia of the corpus callosum. In 66 % of the patients, febrile seizures preceded the onset of epilepsy, which spanned from infancy to adolescence (range=14 months-13 years). Absences (66 %) and focal motor seizures (50 %) were common. No patient met the criteria for drug-resistance. Peculiar electroencephalographic features arose after the epilepsy onset and persisted at long-term follow-up: bilateral and asynchronous focal discharges combined with independent diffuse spike-wave-discharges (100 %) and reflex abnormalities (66 %). ConclusionIn AP-4 complex disease, epilepsy could arise beyond early infancy, until adolescence, with variable combination of generalized and focal seizures. The prognosis was favourable. We observed a common electroencephalographic signature - combined focal/generalized and reflex abnormalities - which may constitute a biomarker of AP-4 deficiency with epilepsy, applicable to inform genetic testing and disentangle the differential diagnosis.

Left hemispheric epilepsy is more frequent and has worse clinical course that right hemispheric epilepsy

IntroductionFew studies demonstrated that focal epilepsy (FE) with left hemispheric (LH) seizure onset is more frequent than with right hemispheric (RH) seizure onset. In addition, patients with LH seizure onset show worse clinical course compared to those with RH seizure onset. The aim of our study was to investigate both issues in a great cohort of FE patients. MethodsIn the retrospective study, we reviewed the clinical and paraclinical data of 682 patients with exclusively LH or RH seizure onset. We ascertained the laterality of seizure onset mainly by ictal and postictal semiology and ictal EEG findings. In the absence of ictal data, the basis of lateralization was the evidence of unilateral structural brain abnormality together with a corresponding interictal EEG finding. The endpoint of analysis of the clinical course was the presence/absence of five-year remission on drug treatment in the first ten years of treatment. ResultsOut of the 682 patients, 378 (55.4 per cent) had LH and 304 (44.6 per cent) had RH seizure onset. The difference was statistically significant (p = 0.04). Out of them, 213 LH and 156 RH patients were eligible to evaluate prognosis. Five-years-remission was attained by 71 patients (33.3 per cent) in the LH, and 65 (41.7 per cent) in the RH group. The difference was statistically significant (p = 0.05). ConclusionWe demonstrated the LH dominance of seizure onset and the worse clinical course of the patients with LH seizure onset. The findings are manifestations of the lateralized epileptic propensity of the brain. The dissimilar clinical course of the patient with LH and RH seizure onset may shape the general prognostic scheme in FE patients.